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Remission of Diabetes after Bariatric Surgery: Results of Randomized Trials
Stacy Brethauer, MD Bariatric and Metabolic Institute
Cleveland Clinic Cleveland, OH
Disclosures
• Ethicon Endo-Surgery Speaker, Research
• Covidien Speaker
• EndoBetix Consultant
Bariatric Surgery Worldwide
Buchwald et al. Obes Surg Jan 2013
U.S. Bariatric Numbers Estimation
2011 2012 2013
Total 158,000 173,000 179,000
RNY 36.7% 37.5% 34.2%
Band 35.4% 20.2% 14%
Sleeve 17.8% 33% 42.1%
BPD/DS 0.9% 1% 1%
Revisions 6% 6% 6%
Other 3.2% 2.3% 2.7%
Bariatric Surgery vs. Intensive Medical
Therapy in Obese Diabetic Patients:
Philip R Schauer, Deepak L Bhatt, John P Kirwan, Kathy Wolski,
Stacy A Brethauer, Sankar D Navaneethan, Ali Aminian,
Claire E Pothier, Ester SH Kim, Steve E Nissen, and Sangeeta R Kashyap
STAMPEDE investigators
3-Year Outcomes
of the STAMPEDE Trial
Cleveland Clinic Bariatric and Metabolic Institute
Endocrinology, Diabetes and Metabolism
Intensive Medical Therapy
• Weight management with diet and lifestyle
counseling per ADA clinical care guidelines*
• Insulin sensitizers, GLP-1 agonists, sulfonylureas
and multiple insulin injections utilized to target
HbA1c ≤6%
• Scheduled visits with nutrition, psychology and
endocrinology per protocol
• Follow-up visits every 3 months through year 2, and
every 6 months for remaining follow up
*Standards of medical care in diabetes--2011. Diabetes Care;34 Suppl 1:S11-61
218 patients screened
50 Intensive medical
therapy alone
50 Medical therapy
plus sleeve gastrectomy
Population for 3-Year Analysis 40 48 49
150 randomized
STAMPEDE Trial: Flow of Patients
50 Medical therapy
plus gastric bypass
1 withdrew consent prior to surgery
8 withdrew consent 2 Lost to follow-up
• HbA1c >7.0%
• BMI 27- 43 kg/m2
• Age 20-60 years
91% retention
2 Lost to follow-up
Primary and Secondary Endpoints at 36 Months
Parameter
Medical
Therapy
(n=40)
Bypass
(n=48)
Sleeve
(n=49)
P
Value1
P
Value2
HbA1c ≤ 6% 5% 37.5% 24.5% <0.001 0.012
HbA1c ≤ 6%
(without DM meds) 0% 35.4% 20.4% <0.001 0.002
HbA1c ≤ 7% 40% 64.6% 65.3% 0.02 0.02
Change in FPG (mg/dL) -6 -85.5 -46 0.001 0.006
Relapse of glycemic
control 80% 23.8% 50% 0.03 0.34
% change in HDL +4.6 +34.7 +35.0 <0.001 <0.001
% change in TG -21.5 -45.9 -31.5 0.01 0.01
% change in CIMT 0.048 0.013 0.017 0.36 0.49
1 Gastric Bypass vs Medical Therapy; 2 Sleeve vs Medical Therapy
0.0
-0.5
-1.0
-1.5
-2.0
-2.5
-3.0
-3.50 3 6 12 24 36
0.0
-0.5
-1.0
-1.5
-2.0
-2.5
-3.0
-3.50 3 6 12 24 36
Change in HbA1c
Change in
HbA1c (%)
P<0.001
P<0.001
Medical
Sleeve
Gastric Bypass
V a l u e a t V i s i t B a s e l i n e M o n t h 6 M o n t h 1 2 M o n t h 2 4 M o n t h 3 6 M e d i c a l 9 . 0 ( 8 . 5 ) 7 . 1 ( 6 . 8 ) 7 . 5 ( 6 . 9 ) 7 . 7 ( 7 . 3 ) 8 . 4 ( 7 . 6 ) G a s t r i c B y p a s s 9 . 3 ( 9 . 2 ) 6 . 3 ( 6 . 2 ) 6 . 3 ( 6 . 1 ) 6 . 5 ( 6 . 4 ) 6 . 7 ( 6 . 6 ) S l e e v e 9 . 5 ( 8 . 9 ) 6 . 7 ( 6 . 4 ) 6 . 6 ( 6 . 4 ) 6 . 8 ( 6 . 8 ) 7 . 0 ( 6 . 6 )
V a l u e a t V i s i t B a s e l i n e M o n t h 6 M o n t h 1 2 M o n t h 2 4 M o n t h 3 6 M e d i c a l 9 . 0 ( 8 . 5 ) 7 . 1 ( 6 . 8 ) 7 . 5 ( 6 . 9 ) 7 . 7 ( 7 . 3 ) 8 . 4 ( 7 . 6 ) G a s t r i c B y p a s s 9 . 3 ( 9 . 2 ) 6 . 3 ( 6 . 2 ) 6 . 3 ( 6 . 1 ) 6 . 5 ( 6 . 4 ) 6 . 7 ( 6 . 6 ) S l e e v e 9 . 5 ( 8 . 9 ) 6 . 7 ( 6 . 4 ) 6 . 6 ( 6 . 4 ) 6 . 8 ( 6 . 8 ) 7 . 0 ( 6 . 6 )
Change in Body Mass Index
Change
in BMI
(Kg/M2)
-12.0
-10.0
-8.0
-6.0
-4.0
-2.0
0.0
-12.0
-10.0
-8.0
-6.0
-4.0
-2.0
0.0
90 3 6 12 24 360 3 6 12 24 369
P=0.006
P<0.001
P<0.001
Value at Visit Baseline Month 6 Month 12 Month 24 Month 36Medical 36.4 34.6 34.2 35.0 34.8Gastric Bypass 37.1 28.2 26.7 27.3 27.9Sleeve 36.1 28.3 27.1 27.9 29.2
Value at Visit Baseline Month 6 Month 12 Month 24 Month 36Medical 36.4 34.6 34.2 35.0 34.8Gastric Bypass 37.1 28.2 26.7 27.3 27.9Sleeve 36.1 28.3 27.1 27.9 29.2
Medical
Sleeve
Gastric Bypass
0
10
20
30
40
50
60
Baseline Month 3 Month 6 Month 12 Month 24 Month 360
10
20
30
40
50
60
Baseline Month 3 Month 6 Month 12 Month 24 Month 36
Percentage of Patients on Insulin
% Patients
Medical 52 54 44 40 47 55
Gastric Bypass 46 25 10 4 7 6
Sleeve 45 16 6 8 9 8
Medical
Sleeve
Gastric Bypass
Cardiovascular Medications at
Baseline and Month 36
CV medications – number
(%)
Medical Therapy
(n=40)
Bypass
(n=48)
Sleeve
(n=49)
Baseline
None 0 (0) 3 (6.3) 2 (4.1)
1 - 2 19 (47.5) 17 (35.4) 28 (57.1)
> 3 21 (52.5) 28 (58.3) 19 (38.8)
Month 36
None 1 (2.5) 33 (68.8) * 21 (42.9) *
1 - 2 18 (45) 14 (29.2) 25 (51)
> 3 21 (52.5) 1 (2.1) 3 (6.1)
* P value <0.05 with Medical Therapy group as comparator
Is Surgery Effective in Patients
with BMI < 35?
• Most Patients with T2DM have BMI 25-35 (60%)
•Currently Metabolic Surgery restricted to BMI ≥ 35
• STAMPEDE-36% of Patients with BMI <35
BMI < 35 vs. BMI ≥ 35
Change in HbA1c
BMI < 35 vs. BMI ≥ 35
Change in BMI
Quality of Life
Physical Functioning
Role Limitations
Physical Health Components
Mental Health Components
** **
* <0.05 ** <0.001 (Compared to IMT)
**
*
*
%
%
Summary: QOL Changes
• Gastric Bypass: 5/8 domains improved
• Sleeve Gastrectomy: 2/8 domains improved
• Intensive Med Rx: 0/8 domains improved
Adverse Events through 36 Months
Parameter Medical Therapy
(n=43)
Bypass
(n=50)
Sleeve
(n=49)
GI complications 2 (5) 13 (26) 5 (4)
Re-op 0 2(4) 2(4)
Stroke 0 0 1 (2)
Retinopathy 0 1 (2) 2 (4)
Nephropathy 4 (9) 7 (14) 5 (10)
Foot ulcers 0 2 (4) 1 (2)
Excessive weight gain 7 (16) 0 0
Gastric Bypass vs Sleeve Gastrectomy
• Study not sufficiently powered to detect modest differences between RYGB and LSG
• Results favoring RYGB over LSG
– Greater success achieving A1c <7.0% without meds
– Greater reduction in DM and CV medications
– Greater reduction in wt. loss
– Greater improvement in Quality of life
• Results favoring LSG over RYGB - None
• 60 patient RCT LRYGB v LSG v IMT
• Baseline A1C 9.7%
• Mean BMI 37
• Beta cell function (mixed meal tolerance)
• Body composition
• 12 and 24 months
Stampede Metabolic Substudy BMI IMT
N=17 RYGB N=18
LSG N-19
P value IMT v RYGB
P value IMT v LSG
P value RYGB
v LSG
Baseline 35.8 36.1 36.4 0.74 0.57 0.77
24 Months 35.6 27.4 28.2 <0.001 <0.001 0.46
Change from Baseline
-0.2 -8.7 -8.2 <0.001 <0.001 0.66
Truncal Fat
Baseline 49.1 50.0 51.8 0.59 0.07 0.27
24 Months 50.0 34.1 41.7 <0.001 <0.001 0.006
Change from Baseline
0.9 -15.9 -10.1 <0.001 <0.001 0.04
Stampede Metabolic Substudy IMT N=17
RYGB N=18
LSG N=19
P value IMT v RYGB
P value IMT v LSG
P value RYGB v LSG
HbA1c < 6% 24 mos
1/17 (6%)
6/18 (33%)
2/19 (10%)
0.09 1.00 0.12
HbA1c Baseline
9.5 9.8 9.7 0.54 0.74 0.84
HbA1c 24 mos
8.4 6.7 7.1 0.01 0.04 0.18
FBG 24 mos (change from baseline)
134 (-33)
87 (-124)
104 (-70)
0.03 0.001
0.04 0.31
0.34 0.03
N using insulin 24 mos
10 (59%) 1 (6%) 2 (11%) 0.001 0.003 1.0
• Insulin Sensitivity (Matsuda Index) – 2.7-fold increase after RYGB
– 1.2-fold increase after LSG
– No change with IMT
• Pancreatic Hormonal Function (oral disposition index = secretion /resistance) – Markedly greater in RYGB compared to IMT
– Correlated with change in % of truncal fat
– No difference between LSG and IMT
Stampede Metabolic Substudy
• Incretin Responses
– Increased postprandial GLP-1 with RYGB, LSG
– GIP decreased in RYGB, no change with LSG
Stampede Metabolic Substudy
Stampede Metabolic Substudy
• Gastric bypass patients maintained near-normal glucose tolerance
• Associated with 5.8-fold increase in overall beta-cell function
• In gastric bypass pts, both insulin sensitivity and secrection increased
• Despite comparable weight loss in LSG, insulin sensitivity was only partially restored and beta cell function did not improve
NEJM 2012
Mingrone et al NEJM 2012
Bariatric surgery versus non-surgical treatment for obesity: a systematic review and meta-analysis of randomised controlled trials Viktoria L Gloy et al. BMJ 2013;347:bmj.f5934
©2013 by British Medical Journal Publishing Group
Mean change in body weight (kg) after bariatric surgery versus non-surgical treatment
(control) for obesity.
Viktoria L Gloy et al. BMJ 2013;347:bmj.f5934
©2013 by British Medical Journal Publishing Group
Type 2 diabetes remission after bariatric surgery versus non-surgical treatment (control) for
obesity.
Viktoria L Gloy et al. BMJ 2013;347:bmj.f5934
©2013 by British Medical Journal Publishing Group
Metabolic syndrome remission after bariatric surgery versus non-surgical treatment (control)
for obesity.
Viktoria L Gloy et al. BMJ 2013;347:bmj.f5934
©2013 by British Medical Journal Publishing Group
• This meta-analysis of randomised controlled trials provides summary effect estimates comparing bariatric surgery with non-surgical treatment for obesity on many different health outcomes
• Bariatric surgery is more effective in inducing body weight loss and remission of type 2 diabetes and metabolic syndrome. There were no perioperative deaths or cardiovascular events reported after bariatric surgery. The most common adverse events after bariatric surgery were iron deficiency anaemia (15%) and reoperations (8%)
• The lack of evidence beyond two years’ follow-up, in particular on adverse events, cardiovascular diseases, and mortality calls for further research
Conclusion
• Current randomized studies favor bypass procedures over sleeve for control of severe diabetes
• Weight loss outcomes vary, but medium-term outcomes favor RYGB and DS
• Metabolic effects: LSG < RYGB < DS
• Risk/Benefit analysis must still be patient-specific
Thank You